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EliA ß2-Glycoprotein I IgA is intended for the in vitro semi-quantitative measurement of IgA antibodies directed to ß2-Glycoprotein I in human serum and plasma (Li-heparin, EDTA) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA B2-Glycoprotein I IgA uses the EliA IgA method on the instrument Phadia 2500/5000.

EliA Cardiolipin IgA is intended for the in vitro sem-quantitative measurement of IgA antibodies directed to cardiolipin in human serum and plasma (Li-heparin, EDTA) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA Cardiolipin IgA uses the EliA IgA method on the instrument Phadia 2500/5000.

The method-specific reagents are identical with K112414 (EliA B2-Glycoprotein I IqA) and K131821 (EliA Cardiolipin IqA), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of:
-Test Wells: EliA ß2-Glycoprotein I IqA Wells are coated with human ß2-Glycoprotein I antigen - 2 carriers (12 wells each), ready to use;

• EliA Cardiolipin IgA Wells are coated with bovine cardiolipin antigen and boyine ß2-glycoprotein I as co-factor - 2 carriers (12 wells each), ready to use;
• -EliA Sample Diluent: PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 6 bottles, 48 mL each, ready to use; or 6 bottles, 400 mL each, ready to use;
• -EliA IqA Conjuqate 50 or 200: ß-Galactosidase labeled anti-IgA (mouse monoclonal antibodies) in PBS containing BSA and 0.06% (w/v) sodium azide -6 wedge shaped bottles, 5 mL each, ready to use; or 6 wedge shaped bottles, 19 mL each, ready to use
• EliA IgA Calibrator Strips: Human IgA (0, 0.3, 1.5, 5, 15, 80 µg/L) in PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 5 strips, 6 singleuse vials per strip, 0.3 mL each, ready to use;
• -EliA IgA Curve Control Strips: Human IgA (20 µg/L) in PBS containing BSA, detergent and 0.095% (w/v) sodium azide – 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use;
• -EliA IgA Calibrator Well: Coated with mouse monoclonal antibodies - 4 carriers (12 wells each), ready to use,

The Phadia EliA Immunodiagnostic System is an automated system for immunodiagnostic testing. The EliA reagents are available as modular packages, each purchased separately. All packages are required to carry out EliA ß2-Glycoprotein I IgA and EliA Cardiolipin IgA tests.

Here's a breakdown of the acceptance criteria and study particulars for the EliA Beta2-Glycoprotein I IgA and EliA Cardiolipin IgA Immunoassays on the Phadia 2500/5000 instrument, based on the provided FDA 510(k) summary (K181329):

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria provided in the document are primarily for method comparison (regression analysis against the predicate device/instrument) and for the performance metrics of Positive Percent Agreement (PPA), Negative Percent Agreement (NPA), and Total Percent Agreement (TPA) when comparing the new instrument platforms (Phadia 2500/5000) to the predicate Phadia 250.

EliA ß2-Glycoprotein I IgA on Phadia 2500/5000

EliA Cardiolipin IgA on Phadia 2500/5000

Note: The document primarily outlines how the studies were performed and what the results were, rather than explicit pre-defined quantitative acceptance criteria for all metrics. For method comparison, it states: "The acceptance criteria for the method comparison (the slope for the regression lines should be 0.9 - 1.1 for single replicate to single replicate and intercept close to 0) were met." For LoQ, it mentions "a target uncertainty goal of 20%." For PPA/NPA/TPA, the high reported values and FDA clearance imply acceptance.

2. Sample Size and Data Provenance for Test Set

• Method Comparison (Instrument Comparison):

  • Sample Size: More than 100 serum samples (for each immunoassay).
  • Data Provenance: Not explicitly stated, but serum samples were used. It is implied to be from patient populations relevant to the intended use. The samples included "≥20% of the samples within ±25% of the medical decision point," suggesting a distribution covering diagnostically relevant ranges.
  • Retrospective/Prospective: Not specified, but typically such comparison studies use retrospectively collected samples for method validation.

• Precision/Reproducibility:

  • Sample Size: 5 serum samples. Each sample tested in 21 runs (3 instruments x 7 runs) with 4 replicates per run, totaling 84 replicates per serum sample.
  • Data Provenance: Serum samples. Country of origin not specified.
  • Retrospective/Prospective: Retrospective, as these are pre-collected serum samples.

• Linearity/Assay Reportable Range:

  • Sample Size: 4 patient serum samples.
  • Data Provenance: Patient serum samples. Country of origin not specified.
  • Retrospective/Prospective: Retrospective.

• Detection Limit (LoB, LoD, LoQ):

  • Sample Size:
    • LoB: One blank sample measured in 33 replicates in each of two runs.
    • LoD & LoQ: Three low-level serum samples measured in 11 replicates in each of two runs.
  • Data Provenance: Blank samples and low-level serum samples. Country of origin not specified.
  • Retrospective/Prospective: Retrospective.

3. Number of Experts and Qualifications for Ground Truth for the Test Set

• This device is an in-vitro diagnostic (IVD) immunoassay, not an AI or imaging device requiring human expert adjudication for ground truth. The "ground truth" for these studies refers to the reference method's result (e.g., predicate device Phadia 250 for method comparison) or the known characteristics of the samples (e.g., spiking for linearity, known concentration for precision controls).
• Therefore, the concept of "number of experts" or their "qualifications" for establishing ground truth in the context of an IVD assay's analytical performance studies is not applicable here.

4. Adjudication Method for the Test Set

• Not applicable as this is an IVD immunoassay, not an AI or imaging device requiring human subjective interpretation and adjudication. The "adjudication" is based on instrumental readings and comparison to defined calibrators and predicate device results.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No, an MRMC comparative effectiveness study was not done. This is an IVD immunoassay, not a device that involves human "readers" interpreting cases in the context of medical imaging or clinical decision-making with or without AI assistance.
• The study involved comparing instrumental results of the new Phadia 2500/5000 platform to the predicate Phadia 250 platform.

6. Standalone Performance Study

• Yes, standalone performance studies were done. The precision, linearity, and detection limit studies are examples of standalone performance evaluations of the EliA immunoassays on the Phadia 2500/5000 instrument.
• The primary scope of this 510(k) submission was to introduce these previously cleared assays onto a new instrument platform (Phadia 2500/5000), meaning the "algorithm" (assay chemistry and measurement principle) itself was already established as effective and safe. The studies here demonstrate that this established assay performs equivalently on the new instrument.

7. Type of Ground Truth Used

• Method Comparison: The predicate device's results (EliA ß2-Glycoprotein I IgA on Phadia 250 instrument, K112414; EliA Cardiolipin IgA on Phadia 250 instrument, K131821) served as the "ground truth" or reference for assessing equivalence of the new instrument platform.
• Precision and Linearity: The values obtained from the predicate device or a well-characterized reference are used to establish control ranges and expected values. For linearity, known dilutions are used against expected concentrations.
• Detection Limit: Controlled blank samples and low-level spiked/characterized samples are used.
• Clinical Studies (reference): For clinical utility and cut-off determination mentioned as reviewed in K112414 and K131821, the ground truth would have been clinical diagnosis (e.g., confirmed APS or SLE) and outcomes data. This summary itself does not include new clinical ground truth studies for K181329.

8. Sample Size for the Training Set

• This type of submission (510(k) for a new instrument platform for existing assays) generally does not involve a "training set" in the context of machine learning or AI.
• For IVD assays, optimization and method development would involve numerous samples, but these are part of product development rather than a formal "training set" that would be distinct from a "test set" in the way AI/ML studies define them. The stability and calibration curves are established using a series of known calibrators and controls.

9. How the Ground Truth for the Training Set Was Established

• Not applicable in the AI/ML sense. For standard IVD assay development, ground truth for calibrators and controls is established through rigorous characterization, often against international reference materials or highly purified substances, and validated using established analytical methods and statistical approaches. The clinical cut-offs were derived from "clinical studies (s. K112414 and K131821)", meaning the previous submissions involved clinical data and patient diagnoses to define the clinically relevant ranges.

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1. Enzyme-linked immunosorbent assay (ELISA) for the qualitative or semi-quantitative detection of β2-GPI IgA antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings.

2. Enzyme-linked immunosorbent assay (ELISA) for the qualitative or semi-quantitative detection of β2-GPI IgG antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings.

3. Enzyme-linked immunosorbent assay (ELISA) for the qualitative or semi-quantitative detection of β2-GPI IgM antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings.

4. Enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of β2-GPI IgA, IgG and IgM antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings.

The test is performed as a solid phase immunoassay (ELISA) in B2GP1 coated microwells. Controls, Calibrators and patient serum samples are incubated in the antigen coated microwells to allow antibodies present in the serum to bind. Unbound antibody and other serum proteins are removed by washing the microwells are detected by adding an enzyme labeled anti-human lgA, lgG, lgM or lgA/IgG/IgM conjugate to the microwells. These enzyme conjugated antibodies bind specifically to the human immunoglobulin of the apropriate class. Unbound enzyme-labeled conjugate is removed by washing. Specific enzyme substrate (TMB) is then added to the presence of antibodies is detected by a color change produced by the conversion of the TMB substrate. The reaction is stopped and the intensity of color change, which is proportional to the concentration of antibody, is read by a spectrophotometer at 450 nm. Results are expressed in ELISA units per milliliter (EU/ml).

Here's a breakdown of the acceptance criteria and study information for the Immulisa Enhanced™ B2GP1 Antibody ELISA devices, based on the provided text:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied by the reported performance in the method comparison study, where the device's agreement with a predicate device is evaluated. The FDA often evaluates substantial equivalence based on such comparisons. Specific pre-defined thresholds for agreement (e.g., >90% overall agreement) are likely part of the internal acceptance criteria, though not explicitly stated as "acceptance criteria" here.

Study Details

1. Sample size used for the test set and the data provenance:

   • Method Comparison (Test Set for Equivalence):
     • IgA: 328 samples (115 Pos, 213 Neg by predicate)
     • IgG: 338 samples (77 Pos, 261 Neg by predicate)
     • IgM: 355 samples (120 Pos, 235 Neg by predicate)
     • IgA/IgG/IgM: 331 samples (177 Any Pos, 154 All Neg by predicate)
   • Cross-Reactivity (Test Set):
     • Various sample sizes depending on the condition, ranging from 7 to 60 for individual Ig classes, and 7 to 45 for the combined IgA/IgG/IgM assay.
   • Clinical Performance (Test Set):
     • The exact total number of clinical samples for APS, APS with SLE, and SLE is not explicitly stated, but the sensitivity and specificity are provided, implying a sufficient number were tested. The percentages are accompanied by 95% Confidence Intervals.
   • Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be retrospective as they involve testing existing clinical samples and disease controls.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • The document implies that the ground truth for the method comparison study was established using a predicate device (INOVA QUANTA Lite™ ß2 GPI IgA, IgG, IgM and Screen ELISA).
   • For the clinical performance studies, the ground truth for "APS," "APS with SLE," and "SLE" diagnoses would typically be established by clinical diagnostic criteria, likely involving an expert consensus based on patient history, other laboratory tests, and clinical findings, but the number and qualifications of experts are not specified in this document.

3. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

   • For the method comparison, the predicate device served as the reference standard, so no human adjudication method (like 2+1) is indicated for the test set results.
   • For clinical performance, the ground truth regarding the disease status (APS, SLE, etc.) would be based on established diagnostic criteria, implying a form of clinical consensus and data, but a specific "adjudication method" involving multiple readers for interpreting the device's results is not mentioned.

4. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

   • No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic (ELISA) kit, not an AI-assisted diagnostic tool that requires human interpretation of images or complex data where AI might "assist" a human reader. Therefore, this question is not applicable to this type of device.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

   • Yes, standalone performance was done. The device itself is the standalone "algorithm" (the ELISA assay) that produces a numerical result (EU/ml) or a qualitative (positive/negative) call. The performance metrics (method comparison, sensitivity, specificity, precision, etc.) all represent the standalone performance of the device.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • Method Comparison: The ground truth was based on the results of a legally marketed predicate device (INOVA QUANTA Lite™ ß2 GPI IgA, IgG, IgM and Screen ELISA).
   • Clinical Performance: The ground truth for disease classifications (APS, APS with SLE, SLE) is implied to be based on clinical diagnostic criteria, which typically involves a combination of clinical findings, patient history, and other laboratory tests (similar to expert consensus/outcomes data). The document states "Sensitivity/specificity exclude healthy human blood on the reference laboratory testing with a possible diagnosis of APS or SLE," indicating samples were classified based on their clinical status.

7. The sample size for the training set:

   • The document does not explicitly state a separate "training set" size for algorithm development. For in-vitro diagnostic assays like ELISAs, assay development and analytical validation typically involve iterative testing with various samples, but these are generally referred to as optimization or development samples, not a distinct "training set" in the context of machine learning. The studies presented (method comparison, clinical performance, etc.) are essentially validation studies, testing the final, developed assay.

8. How the ground truth for the training set was established:

   • As no explicit "training set" is mentioned in the context of algorithm development, similar to machine learning models, this question is not directly applicable. The assay's parameters (e.g., cutoffs, analytical ranges) would have been established during product development using samples whose characteristics (e.g., positive, negative, various concentrations) were known, likely through reference methods or clinical diagnosis, but this is a standard part of ELISA development rather than "ground truth establishment for a training set" as understood in AI/ML.

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The QUANTA Flash® ß2GP1-Domain1 is an in vitro chemiluminescent immunoassay (CIA) for the semi-quantitative determination of IgG autoantibodies to B2GP1-Domain1 in human serum or citrated plasma. The presence of anti-S2GP1-Domain1 autoantibodies is used in conjunction with clinical and other laboratory findings as an aid in the diagnosis of antiphospholipid syndrome. The QUANTA Flash® ß2GP1-Domain1 is not intended to replace assays for antibodies against the whole B2GP1 molecule. Testing for antibodies to the whole is required according to the classification criteria for antiphospholipid syndrome.

The QUANTA Flash® ß2GP1-Domain1 Controls are intended for quality control purposes of the QUANTA Flash® ß2GP1-Domain1 chemiluminescent immunoassay (CIA) kit.

The HemosIL® AcuStar Anti-S2GPI Domain 1 is an in vitro chemiluminescent immunoassay (CIA) for the semiquantitative determination of IgG autoantibodies to 82GPI Domain 1 in human serum or citrated plasma. The presence of anti-ß2GPI Domain 1 autoantibodies is used in conjunction with clinical and other laboratory findings as an aid in the diagnosis of antiphospholipid syndrome. The HemosIL® AcuStar Anti-S2GPI Domain 1 is not intended to replace assays for antibodies against the whole 82GPI molecule. Testing for antibodies to the whole 13GPI molecule is required according to the classification criteria for antiphospholipid syndrome.

The HemosIL AcuStar Anti-B2GPI Domain 1 Controls are intended for quality control purposes of the HemosIL AcuStar Anti-ß2GPI Domain 1 chemiluminescent immunoassay (CIA) kit.

The QUANTA Flash® ß2GP1-Domain1 assay is designed to run on the BIO-FLASH® instrument. This platform is a fully automated closed system with continuous load and random access capabilities that automatically processes the samples, runs the assay and reports the results. It includes liquid handling hardware, luminometer and computer with software-user interface. The QUANTA Flash® ß2GP1-Domain1 assay utilizes a reagent cartridge format, which is compatible with the BIO-FLASH instrument.

The assays included in this submission, the QUANTA Flash ®2GP1-Domain1 marketed by Inova Diagnostics Inc. (9900 Old Grove Road, San Diego, CA 92131) and HemoslL "AcuStar Anti-ß2GPI Domain 1 marketed by Instrumentation Laboratory (180 Hartwell Road Bedford, MA 01730), are equivalent assays. Therefore all data stated hereafter and referred to as: QUANTA Flash ß2GP1-Domain1 data is equivalently also valid for HemosIL * AcuStar Anti-ß2GPI Domain 1.

Recombinant ß2GP1-Domain1 protein is coated onto paramagnetic beads, which are stored lyophilized in the reagent cartridge. The reagent pack is prepared for use in the BIO-FLASH system by pressing down on the grey lid of the reagent pack to pierce the induction seals on the reagent tubes. Once the seals are broken, the beads are rehydrated by adding the entire contents of the vial of resuspension buffer to the bead reagent tube using the transfer pipette supplied with the kit. Only the hole above the bead reagent tube is accessible at this point. The beads are then mixed with the resuspension buffer by pipetting up and down 30 times. This amount of mixing ensures complete resuspension of the beads. The label covering the remaining three reagent holes is now removed, and the reagent cartridge is then loaded onto the BIO-FLASH instrument. Samples are also loaded onto the instrument in sample racks. A patient serum sample is prediluted 1:10 by the BIO-FLASH with system rinse in a small disposable plastic cuvette. Small amounts of the diluted patient serum, the beads, and assay buffer are all combined into a second cuvette, and mixed. This cuvette is then incubated at 37°C. The beads are magnetized and washed several times. lsoluminol conjugated anti-human IgG antibodies are then added to the cuvette, and again incubated at 37°C. The beads are magnetized and washed repeatedly. The isoluminol conjugate is oxidized when Trigger 1 (Fe(III) coproporphyrin in sodium hydroxide solution) and Trigger 2 (urea-hydrogen peroxide in sodium chloride solution) are added to the cuvette, and the flash of light produced from this reaction is measured as Relative Light Units (RLU) by the BIO-FLASH optical system. The RLU are proportional to the amount of isoluminol conjugate that is bound to the human IgG, which is in turn proportional to the amount of anti- ß2GP1-Domain1 antibodies bound to the corresponding ß2GP1-Domain1 on the beads.

The QUANTA Flash® ß2GP1-Domain1 assay utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the reagent cartridge barcode. Every new lot number of reagent cartridge must be calibrated before first use, with the QUANTA Flash® ß2GP1-Domain1 Calibrators. Based on the results obtained with the two Calibrators included in the reagent kit, an instrument specific Working Curve is created, which is used to calculate chemiluminescent units (CU) from the instrument signal (RLU) obtained for each sample.

The QUANTA Flash® ß2GP1-Domain1 kit contains the following materials:

One (1) QUANTA Flash ß2GP1-Domain1 Reagent Cartridge, containing the following reagents for 50 determinations:

• ß2GP1-Domain1 antigen coated paramagnetic beads in a suspension. a.
• b. Assay Buffer – buffer containing protein stabilizers and preservatives.
• C. Tracer IgG - Isoluminol labeled anti-human IgG antibodies in buffer, containing protein stabilizers and preservative.
• d. Sample Diluent - buffer containing protein stabilizers and preservatives.
• d. Resuspension Buffer - buffer containing protein stabilizers and preservatives.
• e. QUANTA Flash ß2GP1-Domain1 Calibrator 1: One (1) barcode labeled tube containing 1.0 mL prediluted, ready to use reagent. Calibrators contain human antibodies to ß2GP1-Domain1 in stabilizers and preservatives.
• f. QUANTA Flash ß2GP1-Domain1 Calibrator 2: One (1) barcode labeled tube containing 1.0 mL prediluted, ready to use reagent. Calibrators contain human antibodies to ß2GP1-Domain1 in stabilizers and preservatives

The QUANTA Flash® ß2GP1-Domain1 Controls kit contains three vials of Low Control and three vials of High Control.

• QUANTA Flash ß2GP1-Domain1 Low Control: Three (3) barcode labeled tubes containing 1.0 mL, ready to use reagent. Controls contain human antibodies to ß2GP1-Domain1 in stabilizers and preservatives.
• QUANTA Flash ß2GP1-Domain1 High Control: Three (3) barcode labeled tubes containing 1.0 mL, ready to use reagent. Controls contain human antibodies to ß2GP1-Domain1 in stabilizers and preservatives.

Here's a breakdown of the acceptance criteria and study details for the QUANTA Flash® ß2GP1-Domain1 device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

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The QUANTA Flash® ß2GP1-Domain1 is an in vitro chemiluminescent immunoassay (CIA) for the semi-quantitative determination of IgG autoantibodies to ß2GP1-Domain1 in human serum. The presence of anti-B2GP1- Domain1 autoantibodies is used in conjunction with clinical and other laboratory findings as an aid in the diagnosis of antiphospholipid syndrome. The OUANTA Flash® B2GP1-Domain1 is not intended to replace assays for antibodies against the whole ß2GP1 molecule. Testing for antibodies to the whole is required according to the classification criteria for antiphospholipid syndrome.

The QUANTA Flash ß2GP1-Domain1 Controls are intended for quality control purposes of the QUANTA Flash ß2GP1-Domain1 chemiluminescent immunoassay (CIA) kit.

The HemosIL® AcuStar Anti-S2GPI Domain 1 is an in vitro chemiluminescent immunoassay (CIA) for the semiquantitative determination of IgG autoantibodies to B2GPI Domain 1 in human serum. The presence of anti-R2GPI Domain 1 autoantibodies is used in conjunction with clinical and other laboratory findings as an aid in the diagnosis of antiphospholipid syndrome. The HemosIL® AcuStar Anti-ß2GPI Domain 1 is not intended to replace assays for antibodies against the whole ß2GPI molecule. Testing for antibodies to the whole is required according to the classification criteria for antiphospholipid syndrome.

The HemosIL AcuStar Anti-B2GPI Domain 1 Controls are intended for quality control purposes of the HemosIL AcuStar Anti-ß2GPI Domain 1 chemiluminescent immunoassay (CIA) kit.

The QUANTA Flash® ß2GP1-Domain1 assay is designed to run on the BIO-FLASH® instrument. This platform is a fully automated closed system with continuous load and random access capabilities that automatically processes the samples, runs the assay and reports the results. It includes liquid handling hardware, luminometer and computer with software-user interface. The QUANTA Flash® ß2GP1-Domain1 assay utilizes a reagent cartridge format, which is compatible with the BIO-FLASH instrument.

The assays included in this submission, the QUANTA Flash ß2GP1-Domain1 marketed by Inova Diagnostics Inc. (9900 Old Grove Road, San Diego, CA 92131) and HemoslL AcuStar Anti-ß-GPI Domain 1 marketed by Instrumentation Laboratory (180 Hartwell Road Bedford, MA 01730), are equivalent assays. Therefore all data stated hereafter and referred to as: QUANTA Flash §2GP1-Domain1 data is equivalently also valid for HemosIL "AcuStar Anti-ß₂GPI Domain 1.

Recombinant ß2GP1-Domain1 protein is coated onto paramagnetic beads, which are stored lyophilized in the reagent cartridge. The reagent pack is prepared for use in the BIO-FLASH system by pressing down on the grey lid of the reagent pack to pierce the induction seals on the reagent tubes. Once the seals are broken, the beads are rehydrated by adding the entire contents of the vial of resuspension buffer to the bead reagent tube using the transfer pipette supplied with the kit. Only the hole above the bead reagent tube is accessible at this point. The beads are then mixed with the resuspension buffer by pipetting up and down 30 times. This amount of mixing ensures complete resuspension of the beads. The label covering the remaining three reagent holes is now removed, and the reagent cartridge is then loaded onto the BIO-FLASH instrument. Samples are also loaded onto the instrument in sample racks. A patient serum sample is prediluted 1:10 by the BIO-FLASH with system rinse in a small disposable plastic cuvette. Small amounts of the diluted patient serum, the beads, and assay buffer are all combined into a second cuvette, and mixed. This cuvette is then incubated at 37°C. The beads are magnetized and washed several times. Isoluminol conjugated anti-human IgG antibodies are then added to the cuvette, and again incubated at 37°C. The beads are magnetized and washed repeatedly. The isoluminol conjugate is oxidized when Trigger 1 (Fe(III) coproporphyrin in sodium hydroxide solution) and Trigger 2 (urea-hydrogen peroxide in sodium chloride solution) are added to the cuvette, and the flash of light produced from this reaction is measured as Relative Light Units (RLU) by the BIO-FLASH optical system. The RLU are proportional to the amount of isoluminol conjugate that is bound to the human IgG, which is in turn proportional to the amount of anti- ß2GP1-Domain1 antibodies bound to the corresponding ß2GP1-Domain1 on the beads.

The QUANTA Flash® ß2GP1-Domain1 assay utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the reagent cartridge barcode. Every new lot number of reagent cartridge must be calibrated before first use, with the QUANTA Flash® ß2GP1-Domain1 Calibrators. Based on the results obtained with the two Calibrators included in the reagent kit, an instrument specific Working Curve is created, which is used to calculate chemiluminescent units (CU) from the instrument signal (RLU) obtained for each sample.

This document describes the analytical and clinical performance characteristics of the QUANTA Flash® β2GP1-Domain1 and HemosIL® AcuStar Anti-β2GPI Domain 1 assays, which are in vitro chemiluminescent immunoassays (CIA) for the semi-quantitative determination of IgG autoantibodies to β2GP1-Domain1 in human serum, used as an aid in diagnosing antiphospholipid syndrome (APS).

1. Table of Acceptance Criteria and Reported Device Performance

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EliA ß2-Glycoprotein I IgA is intended for the in vitro semi-quantitative measurement of IgA antibodies directed to ß2-Glycoprotein I in human serum and plasma (heparin, EDTA, citrate) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA ß2-Glycoprotein 1 IgA uses the EliA IgA method on the instruments Phadia 100 and Phadia 250.

The new device belongs to a fully integrated and automated system for immunodiagnostic testing. It comprises a Fluorescence-Immunoassay test system using EliA single wells as the solid phase and is intended to be performed on the instruments Phadia 100 and Phadia 250.

The conjugate for the EliA IgA method is mouse anti-human IgA beta-galactosidase, which uses 4-Methylumbelliferyl-BD-Galactoside as substrate.

The total IgA calibration is based on a set of six WHO-standardized IgA Calibrators derived from human serum. They are used to establish an initial calibration curve, which may be used for up to 28 days on additional assays and can be stored by the instrument. Each additional assay includes calibrator (curve) controls that have to recover in defined ranges to ensure that the stored calibration curve is still valid. The Fluorescence-Immunoassay test system includes test-specific, method-specific and general reagents that are packaged as separate units.

Here's a breakdown of the acceptance criteria and study information for the EliA™ ß2-Glycoprotein I IgA Immunoassay, based on the provided 510(k) summary:

The provided 510(k) summary primarily focuses on establishing "substantial equivalence" to a predicate device for this in vitro diagnostic (IVD) immunoassay, rather than presenting a performance study with detailed acceptance criteria in the manner one might see for an AI/software device or a medical imaging device. The "performance" here relates to how well the new device compares to the predicate and its ability to detect the target antibodies.

1. Table of Acceptance Criteria and the Reported Device Performance

• Comparison study between new and predicate device
• Results from clinically defined sera
• Results from samples of apparently healthy subjects (normal population)
  Overall Finding: All available data support the new device is substantially equivalent to the predicate device. |
  | Intended Use | Semi-quantitative measurement of IgA antibodies directed to ß2-Glycoprotein I to aid in diagnosis of antiphospholipid syndrome (APS) and thrombotic disorders related to systemic lupus erythematosus (SLE). | The device's performance supports its intended use as described. |
  | Method | Uses EliA IgA method on Phadia 100 and Phadia 250 instruments. | The device is designed to operate with these instruments and methods. |
  | Calibration | IgA calibration based on six WHO-standardized IgA Calibrators; initial calibration curve valid for up to 28 days; includes calibrator (curve) controls with defined recovery ranges. | The system incorporates this calibration method to ensure validity and accuracy. |

Explanation of "Acceptance Criteria" for IVDs in a 510(k) context: For an in vitro diagnostic device seeking 510(k) clearance, acceptance criteria often revolve around demonstrating analytical and clinical performance comparable to a legally marketed predicate device. This typically involves studies on precision, accuracy (comparison to a reference method or predicate), linearity, detection limits, interference, and agreement studies for clinical samples. The provided summary is very high-level and only states that data supports equivalence, rather than detailing specific numerical criteria used in those studies (e.g., "agreement rate >90%").

2. Sample Size Used for the Test Set and Data Provenance

The summary does not provide specific sample sizes for the "test set" or explicit data provenance (e.g., country of origin). It generally refers to:

• "results obtained within a comparison study between new and predicate device"
• "results obtained for clinically defined sera"
• "results obtained for samples from apparently healthy subjects (normal population)"

This indicates the data was collected retrospectively from various sample sources to facilitate comparison. Without more detail, it's not possible to determine if the samples were prospective.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This information is not provided in the summary. For an IVD, "ground truth" (or clinical truth) for samples used in method comparison or clinical concordance studies would typically be established by combining patient clinical diagnoses (e.g., diagnosed with APS or SLE by a rheumatologist/hematologist) with results from established, often predicate, diagnostic tests. The summary implies "clinically defined sera" were used, meaning these samples had a known clinical status, but the process of establishing that status (e.g., number and qualifications of clinicians) is not detailed.

4. Adjudication Method for the Test Set

This information is not provided in the summary. For IVDs, adjudication isn't typically used in the same way as for imaging devices where multiple readers interpret images. Instead, the "ground truth" for clinical samples is based on a patient's overall clinical presentation and diagnosis, typically accepted as definitive for the study.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for medical imaging AI devices where human readers interpret images. The EliA™ ß2-Glycoprotein I IgA Immunoassay is an in vitro diagnostic (IVD) serological test, not an imaging device, and does not involve human "readers" interpreting results in a way that an MRMC study would be applicable.

6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done

This refers to the performance of the immunoassay system itself. The device is described as a "fully integrated and automated system for immunodiagnostic testing" and requires operation on the "Phadia 100/Phadia 250" instruments which include "software for evaluation of test results." Therefore, its performance is inherently "standalone" in the sense that the instrument-software system processes the sample and yields a result without direct human interpretation of a raw signal. The comparison studies described are essentially evaluating this standalone performance against the predicate.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The summary implies two types of "ground truth" for the performance studies:

• Predicate Device Results: For the "comparison study between new and predicate device," the predicate device's results (Varelisa ß2-Glycoprotein I IgA Antibodies, K040450) would serve as a comparative ground truth.
• Clinical Diagnoses: For "clinically defined sera," the ground truth would be the clinical diagnosis of the patient (e.g., presence or absence of APS or SLE-related thrombotic disorders), presumably based on a combination of clinical symptoms, other laboratory findings, and expert physician assessment. The "samples from apparently healthy subjects" provide a "negative" ground truth based on their healthy status.

8. The Sample Size for the Training Set

The summary does not mention a training set in the context of machine learning or AI. This device is an immunoassay, not an AI or machine learning device that requires a separate training phase. The "calibration" of the device is based on a set of WHO-standardized IgA Calibrators, which is distinct from a machine learning training set.

9. How the Ground Truth for the Training Set was Established

As no training set (in the machine learning sense) is discussed, this question is not applicable. The "ground truth" for the calibration is established by using "WHO-standardized IgA Calibrators derived from human serum," implying these calibrators have a known and certified IgA concentration.

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HemosILTM AcuStar Anti-ß2 Glycoprotein-I IgG: Fully automated chemiluminescent immunoassay for . the semi-quantitative measurement of anti-ß, Glycoprotein-I (anti-B>GPI) IgG antibodies in human citrated plasma and serum on the ACL AcuStar, as an aid in the diagnosis of thrombotic disorders related to primary and secondary Antiphospholipid Syndrome (APS) when used in conjunction with other laboratory and clinical findings.
HemosILTM AcuStar Anti-B2 Glycoprotein-I IgM: Fully automated chemiluminescent immunoassay for . the semi-quantitative measurement of anti-B2 Glycoprotein-I (anti-B>GPI) IgM antibodies in human citrated plasma and serum on the ACL AcuStar as an aid in the diagnosis of thrombotic disorders related to primary and secondary Antiphospholipid Syndrome (APS) when used in conjunction with other laboratory and clinical findings.
. HemosIL AcuStar Anti-B2 Glycoprotein-I IgG Controls: For the quality control of the Anti-B2 Glycoprotein-I IgG assay performed on the ACL AcuStar.
. HemosIL AcuStar Anti-B2 Glycoprotein-I IgM Controls: For the quality control of the Anti-B2 Glycoprotein-I IgM assay performed on the ACL AcuStar.

HemosIL AcuStar Anti-B2 Glycoprotein-I IgG is a chemiluminescent two-step immunoassay . consisting of magnetic particles coated with human purified ByGPI which capture, if present, the anti-ByGPI antiphospholipid antibodies from the sample. After incubation, magnetic separation, and a wash step, a tracer consisting of an isoluminol-labeled anti-human IgG antibody is added and may bind with the captured anti-B2GPI IgG on the particles. After a second incubation, magnetic separation, and wash step, reagents that trigger the luminescent reaction are added, and the emitted light is measured as relative light units (RLUs) by the ACL AcuStar optical system. The RLUs are directly proportional to the anti-ß2GPI IgG concentration in the sample.
The ACL AcuStar anti-B2GPI IgG assay utilizes a 4 Parameter Logistic Curve (4PLC) fit data reduction method to generate a Master Curve. The Master Curve is predefined and lot dependent and it is stored in the instrument through the cartridge barcode. With the measurement of calibrators, the predefined Master Curve is transformed to a new, instrument specific 4PLC Working Curve. The concentration values of the calibrators are included in the calibrator tube barcodes.
. HemosIL AcuStar Anti-B2 Glycoprotein-I IgM is a chemiluminescent two-step immunoassay consisting of magnetic particles coated with human purified ByGPI which capture, if present, the anti-B2GPI antiphospholipid antibodies from the sample. After incubation, magnetic separation, and a wash step, a tracer consisting of an isoluminol-labeled anti-human IgM antibody is added and may bind with the captured anti-ß2GPI IgM on the particles. After a second incubation, magnetic separation, and wash step, reagents that trigger the luminescent reaction are added, and the emitted light is measured as relative light units (RLUs) by the ACL AcuStar optical system. The RLUs are directly proportional to the anti-B2GPI IgM concentration in the sample.
The ACL AcuStar anti-B3GPI IgM assay utilizes a 4 Parameter Logistic Curve (4PLC) fit data reduction method to generate a Master Curve. The Master Curve is predefined and lot dependent and it is stored in the instrument through the cartridge barcode. With the measurement of calibrators, the predefined Master Curve is transformed to a new, instrument specific 4PLC Working Curve. The concentration values of the calibrators are included in the calibrator tube barcodes.
HemosIL AcuStar Anti-B2 Glycoprotein-I IgG Controls: The Low and High Anti-S, Glycoprotein-I . IgG Controls are prepared by means of a dedicated process and contain different concentrations of human anti-ß2 Glycoprotein-I IgG antibodies.
. Low Anti-B2 Glycoprotein-I IgG Control: Control intended for the assessment of precision and accuracy of the assay at the normal or around cut-off anti-B2 Glycoprotein-I IgG levels.
. High Anti-B2 Glycoprotein-I IgG Control: Control intended for the assessment of precision and accuracy of the assay at the abnormal anti-B2 Glycoprotein-I IgG levels.
. HemosIL AcuStar Anti-B2 Glycoprotein-I IgM Controls: The Low and High Anti-B2 Glycoprotein-I IgM Controls are prepared by means of a dedicated process and contain different concentrations of human anti-B2 Glycoprotein-I IgM antibodies.
. Low Anti-B2 Glycoprotein-I IgM Control intended for the assessment of precision and accuracy of the assay at the normal or around cut-off anti-B2 Glycoprotein-I IgM levels.
. High Anti-B2 Glycoprotein-I IgM Control: Control intended for the assessment of precision and accuracy of the assay at the abnormal anti-B2 Glycoprotein-I IgM levels.

The provided text describes performance data for the HemosIL AcuStar Anti-B2 Glycoprotein-I IgG and IgM assays, which are in vitro diagnostic (IVD) devices. The acceptance criteria and performance studies for IVDs differ significantly from those for algorithm-based medical devices or AI. Therefore, much of the requested information (like sample size for test set, data provenance, number of experts for ground truth, adjudication method, MRMC studies, standalone performance, and training set details) is not applicable or cannot be directly extracted from this document in the context of an AI/algorithm-based device.

However, I can extract information related to the performance characteristics provided for these IVDs, which serve as their "acceptance criteria" and "proof of meeting acceptance criteria" in the context of a 510(k) submission for an IVD.

Here's the information extracted and adapted where possible:

Acceptance Criteria and Reported Device Performance

For IVD devices like those described, performance is typically assessed through precision, sensitivity, specificity, and agreement with predicate devices or clinical outcomes. The "acceptance criteria" are implicitly met if the reported performance characteristics are deemed sufficient for the device's intended use and demonstrate substantial equivalence to predicate devices during the 510(k) review process.

1. Table of Acceptance Criteria and Reported Device Performance:

2. Sample size used for the test set and the data provenance:

• Clinical Outcome Studies Test Set: 321 frozen citrated plasma samples.
  • Provenance: Samples were "selected" from 6 different groups:
    • Primary APS (PAPS)
    • Secondary APS (SAPS)
    • Systemic Lupus Erythematosus (SLE) but not APS
    • SLE-like
    • Patients with cardiovascular disorders (not classified in the above four groups)
    • Apparently healthy people
  • This implies a retrospective collection of samples, likely from multiple sources within a country or countries (not specified beyond "selected").
• Method Comparison Studies Test Set:
  • IgG: 150 samples (those from the clinical performance study that were within the compared methods' test ranges).
  • IgM: 205 samples (those from the clinical performance study that were within the compared methods' test ranges).
  • Provenance: Same as the clinical outcome studies (retrospective, unspecified country/countries).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

• For IVD devices, "ground truth" is typically established by existing diagnostic criteria (e.g., standard objective tests, clinical diagnosis) or comparison to a gold standard method. In this case, the ground truth for the clinical outcome study groups (PAPS, SAPS, SLE, etc.) was established based on "standard objective tests" and clinical findings. It does not involve a panel of human experts reviewing individual cases directly.
• Therefore, this information (number of experts, qualifications, adjudication method) is not applicable in the context of this IVD submission as it would be for an image-based AI device.

4. Adjudication method for the test set:

• Not applicable for this type of IVD study where ground truth is based on established clinical classifications and standard objective tests, rather than subjective expert review needing adjudication.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

• No, this was not an MRMC study. This is an in vitro diagnostic assay designed to be read by automated equipment (ACL AcuStar) and generate quantitative results, not an AI device assisting human readers in interpreting images or other complex data. This question is not applicable.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

• Yes, this is a standalone performance study. The device itself (HemosIL AcuStar assay on the ACL AcuStar instrument) provides a semi-quantitative measurement of antibodies. The performance metrics presented (precision, sensitivity, specificity, agreement with predicate) are for the device operating independently to produce these measurements. There is no human-in-the-loop component in the direct measurement process. The results are then used by clinicians, but the device's performance is standalone.

7. The type of ground truth used:

• Clinical Diagnosis and Standard Objective Tests: For the clinical outcome studies, the patient groups (PAPS, SAPS, SLE, etc.) were defined based on their clinical diagnosis and results from "standard objective tests." This serves as the clinical ground truth.
• Predicate Device Results: For the method comparison studies, the results of the "REAADS IgG Anti-β2GPI Test Kit" and "REAADS IgM Anti-β2GPI Test Kit" (ELISA assays) served as the comparative ground truth (or reference method).

8. The sample size for the training set:

• Not explicitly stated in this summary. For IVD assays, there isn't a "training set" in the same sense as machine learning. Assay development involves numerous experiments, reagent optimization, and calibration curve generation (which itself uses calibrators and a 4PLC fit model as described). The 4PLC Master Curve is "predefined and lot dependent" and is stored in the instrument, indicating a developmental process to establish this curve. However, a distinct "training set" size for an algorithm is not provided or applicable.

9. How the ground truth for the training set was established:

• Not applicable in the context of an AI training set. For IVD assays, the "ground truth" for developing and calibrating the assay would involve using known-concentration standards (calibrators) and characterized patient samples. The document mentions "calibrators" with "concentration values... included in the calibrator tube barcodes" and a 4PLC data reduction method to generate a "Master Curve," which is "predefined and lot dependent." This process inherently uses reference materials to establish the curve, which is analogous to "ground truth" for the assay's quantitative output.

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The TheraTest EL-β2GPITM (IgM-IgG-IgA) is a set of in vitro diagnostic tests for the measurement of IgM, IgG and IgA autoantibodies in human serum directed against serum beta 2-glycoprotein I (β2GPI). This measurement aids in the diagnosis of antiphospholipid antibody syndrome (APS) or certain autoimmune thrombotic disorders such as those secondary to systemic lupus erythematosus.

The TheraTest EL-32GPI TM Scr is an in vitro diagnostic test for the screening for autoantibodies in human serum directed against the serum glycoprotein beta 2glycoprotein I (B2GPI). This measurcment aids in the diagnosis of antiphospholipid antibody syndrome (APS) or certain autoimmune thrombotic disorders such as those secondary to systemic lupus erythematosus.

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This document is a 510(k) premarket notification for two in vitro diagnostic tests: TheraTest EL-β2GPI™ (IgM-IgG-IgA) and TheraTest EL-β2GPI™ Scr. The FDA has determined these devices are substantially equivalent to legally marketed predicate devices.

However, the provided text does not contain the detailed study information required to fill out the requested table and answer all points about acceptance criteria and device performance. This document primarily focuses on the FDA's decision regarding substantial equivalence based on the 510(k) submission, and not the specific performance study conducted by the manufacturer.

Therefore, I cannot provide a complete answer to your request using only the provided text. The document refers to an "enclosure" which likely contains the performance data, but that enclosure is not part of this input.

A partial response based on what can be inferred from the provided text:

1. A table of acceptance criteria and the reported device performance

• Acceptance Criteria: Not explicitly stated in this document. Often, for 510(k)s, the acceptance criteria relate to demonstrating comparable performance (e.g., sensitivity, specificity, accuracy, precision) to a legally marketed predicate device.
• Reported Device Performance: Not detailed in this document. The document confirms the device is an in vitro diagnostic test for measuring autoantibodies, which "aids in the diagnosis of antiphospholipid antibody syndrome (APS) or certain autoimmune thrombotic disorders." This implies the performance would be measured in terms of its ability to detect these autoantibodies.

2. Sample sized used for the test set and the data provenance

• Sample Size: Not specified in this document.
• Data Provenance: Not specified in this document (e.g., country of origin, retrospective/prospective).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

• Not specified in this document.

4. Adjudication method for the test set

• Not specified in this document.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done

• Not applicable as this is an in vitro diagnostic (assay-based) device, not an imaging device requiring human reader interpretation in the same way.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done

• This is an in vitro diagnostic test, meaning its performance is inherently "standalone" in its measurement of analytes. The "human-in-the-loop" would be the clinician interpreting the test results in the context of other clinical information, not directly interacting with the measurement itself.

7. The type of ground truth used

• For an in vitro diagnostic test for autoantibodies, the ground truth would typically be established through:
  • Clinical diagnosis: Confirmation of APS or autoimmune thrombotic disorders through established clinical criteria, potentially including other laboratory tests and patient history.
  • Reference laboratory methods: Comparison to a gold standard or well-established reference method for autoantibody detection (e.g., western blot, immunofluorescence, or other highly sensitive/specific assays).
  • Outcomes data: Although less common for establishing initial analytical performance, long-term patient outcomes could be part of a broader validation.
  • However, the specific type of ground truth used for this device is not detailed in the provided document.

8. The sample size for the training set

• Not specified in this document.

9. How the ground truth for the training set was established

• Not specified in this document.

To get the full details, you would need to consult the complete 510(k) submission, particularly the "enclosure" mentioned in the letter, which would contain the performance study data.

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An enzyme-linked immunoassay (ELISA) for the detection of IgG antibodies to complexes formed by oxidized low-density lipoprotein (oxLDL) with ß2-glycoprotein I (ß2GPI) in individuals with systemic lupus erythematosus (SLE) and lupus-like disorders (antiphospholipid syndrome).

The IgG Anti-AtherOx Test Kit is an indirect ELISA detecting IgG anti-oxLDL/B2GPI antibodies. Diluted serum samples, calibrator(s), and controls are incubated in microwells coated with the oxLDL-ß2GPI complex. Incubation allows the IgG anti-oxLDL-B2GPI antibody present in the samples to react with the immobilized antigen complex. After the removal of unbound serum proteins by washing, anti-human IgG antibodies, labeled with horseradish peroxidase (HRP), are added forming complexes with the bound IgG anti-oxLDL-B2GPI antibody. Following another washing step, the bound enzyme-antibody conjugate is assayed by the addition of a solution containing tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2) as the chromogenic substrate. Color develops in the wells at an intensity proportional to the serum concentration of IgG anti-oxLDL-B2GPI antibody. Results are obtained by reading the OD (optical density or absorbance) of each well in a spectrophotometer. Calibrator sera are provided, with the IgG anti-oxLDL-B2GPI antibody concentration expressed in G Units. A log-log regression analysis is performed with calibrator values plotted against calibrator mean ODs. Controls and patient results are determined from the calibration curve.

Here's an analysis of the provided 510(k) summary regarding acceptance criteria and the study that proves the device meets those criteria:

The document provided does not contain explicit "acceptance criteria" for clinical performance in the typical sense of metrics like sensitivity, specificity, or agreement thresholds against an established reference standard. Instead, the clinical testing section focuses on demonstrating agreement with a legally marketed predicate device (REAADS IgG Anti-Cardiolipin Test Kit) across various patient populations. Therefore, the "acceptance criteria" are implied by the observed agreement rates with the predicate, rather than set a-priori.

Acceptance Criteria and Reported Device Performance

Given the nature of the submission (demonstrating substantial equivalence to a predicate device), the primary "acceptance criterion" appears to be sufficient agreement with the predicate device across different patient populations.

Study Information:

1. Sample Size used for the test set and the data provenance:

   • Test Set Sample Size: A total of 448 serum samples were tested:
     • 205 from healthy control patients.
     • 99 from patients with rheumatoid arthritis.
     • 143 from patients with systemic lupus erythematosus (SLE).
   • Data Provenance: Not explicitly stated (e.g., country of origin). The study appears to be retrospective as it uses "serum samples from" patients, implying they were collected prior to the study for testing.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • The document does not state that experts were used to establish a "ground truth" for the test set. Instead, the device's performance is compared to a legally marketed predicate device (REAADS IgG Anti-Cardiolipin Test Kit). The predicate device itself serves as the reference for comparison, not an independent expert consensus.

3. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

   • There is no mention of an adjudication method in the context of expert review or ground truth establishment. The comparison is directly between the new device and the predicate device.

4. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, if so, what was the effect size of how much human readers improve with AI vs without AI assistance:

   • This is an in vitro diagnostic (IVD) device (ELISA test kit) for detecting antibodies in serum. It is not an AI-powered diagnostic imaging device or a device involving human readers/interpreters in the presented study. Therefore, an MRMC study or evaluation of human reader improvement with AI assistance is not applicable to this submission.

5. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

   • This is an IVD test kit. The "standalone" performance is essentially what is presented in the study: the direct comparison of the assay's results against the predicate device. There is no human-in-the-loop component in the interpretation of the test results described here beyond the laboratory technician performing the assay and reading the ODs.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • The "ground truth" (or reference standard for comparison) in this 510(k) submission is the performance of the REAADS IgG Anti-Cardiolipin Test Kit, a legally marketed predicate device. The clinical diagnoses of the patients (healthy controls, RA, SLE, APS) serve as classification for the samples, but the direct comparison is test-vs-test.

7. The sample size for the training set:

   • The document does not explicitly mention a "training set" for the purpose of machine learning or algorithm development. This is a traditional ELISA assay kit. The provided clinical study data (448 samples) represent the "test set" for performance evaluation, not a training set. Development and optimization of the assay would typically involve internal validation, but those details are not part of this summary in terms of a "training set" as understood in AI/ML contexts.

8. How the ground truth for the training set was established:

   • As there's no mention of a "training set" in the context of algorithm development, this question is not applicable. The development of the assay itself would have involved establishing specific assay parameters, but the mechanism for doing so isn't detailed as "ground truth establishment" for a training set.

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AESKULISA ß2 Glyco-A is a solid phase enzyme immunoassay employing native ß2 glycoprotein I highly purified from human plasma for the semiquantitative and qualitative detection of IgA antibodies against ß2 glycoprotein I in human serum. The presence of anti-ß2 glycoprotein I antibodies in conjunction with clinical findings and other laboratory results can be used as an aid in the diagnosis of thrombotic disorders related to primary and secondary antiphospholipid syndrome.

AESKULISA ß2 Glyco-GM is a solid phase enzyme immunoassay employing native ß2 glycoprotein I highly purified from human plasma for the separate semiquantitative and qualitative detection of IgG and/or IgM antibodies against β2 glycoprotein I in human serum. The presence of anti-ß2 glycoprotein I antibodies in conjunction with clinical findings and other laboratory results can be used as an aid in the diagnosis of thrombotic disorders related to primary and secondary antiphospholipid syndrome.

AESKULISA ß2 Glyco-Check is a solid phase enzyme immunoassay employing native ß2 glycoprotein 1 highly purified from human plasma for the combined semiquantitative and qualitative detection of IgA, IgG and IgM antibodies against ß2 glycoprotein I in human serum. The presence of anti-ß2 glycoprotein I antibodies in conjunction with clinical findings and other laboratory results can be used as an aid in the diagnosis of thrombotic disorders related to primary and secondary antiphospholipid syndrome.

Not Found

I am sorry, but the provided text does not contain the detailed information necessary to describe the acceptance criteria and the study that proves the device meets them in the format you requested. The document is a 510(k) clearance letter from the FDA, which confirms that the device is substantially equivalent to a legally marketed predicate device. It defines the intended use of the devices (AESKULISA® ß2-Glyco-A, AESKULISA® ß2-Glyco-GM, AESKULISA® ß2-Glyco-Check) for detecting antibodies related to antiphospholipid syndrome.

However, the letter does not include:

1. A table of acceptance criteria and reported device performance.
2. Details about sample size for test sets or their data provenance.
3. Information on the number or qualifications of experts used for ground truth.
4. Adjudication methods.
5. Results of Multi-Reader Multi-Case (MRMC) comparative effectiveness studies.
6. Results of standalone algorithm performance studies.
7. The type of ground truth used (e.g., pathology, outcomes data).
8. The sample size for the training set.
9. How ground truth for the training set was established.

This document serves as a regulatory clearance notice, not a detailed study report or clinical trial summary. To get the information you are looking for, you would typically need to consult the full 510(k) submission, the device's labeling, or peer-reviewed publications related to the device.

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The Varelisa ß2-Glycoprotein I IgA Antibodies EIA kit is designed for the semiquantitative and qualitative determination of ß2-glycoprotein I IgA antibodies in serum or plasma.

The presence of B2-glycoprotein I antibodies can be used in conjunction with clinical findings and other laboratory tests to aid in the diagnosis of thrombotic disorders related to the primary Antiphospholipid Syndrome or occurring secondary to systemic lupus erythematosus (SLE) or other autoimmune diseases.

The Varelisa B2-Glycoprotein I IgA Antibodies EIA kit is designed for the semiquantitative and qualitative determination of ß2-glycoprotein I IgA antibodies in serum or plasma.

The test kit contains microplate strips coated with human purified ß2glycoprotein I, calibrators, positive and negative controls, enzyme-labeled conjugate, substrate and substrate stop solution, buffered diluent and wash buffer.

Here's an analysis of the provided text regarding the Varelisa® ß2 Glycoprotein I IgA Antibodies device, structured to address your specific questions about acceptance criteria and study details.

Please note: The provided text is a 510(k) summary, which often focuses on demonstrating substantial equivalence to a predicate device rather than presenting extensive de novo performance data with detailed acceptance criteria and standalone studies in the way a PMA might. As such, some of your requested information (e.g., specific quantitative acceptance criteria, standalone performance details, MRMC study results) is not explicitly present in the provided document. I will extract what is available and indicate when information is not provided.

Acceptance Criteria and Reported Device Performance

The provided 510(k) summary describes laboratory equivalence to a predicate device. It does not explicitly state quantitative acceptance criteria in a table format with specific thresholds. Instead, it relies on demonstrating comparable performance to the predicate device and expected behavior based on medical literature.

• Results for externally defined calibrators showed comparability.
• Results for samples from apparently healthy subjects (normal population) showed comparability. |
  | Suitability for Serum and Plasma Samples | - The device is outlined for use with serum and plasma, with corresponding performance data underlining its effectiveness with plasma as a sample. |
  | Performance in line with medical literature | - The assay performs as expected from the medical literature regarding the diagnosis of thrombotic disorders related to primary Antiphospholipid Syndrome or secondary to SLE/other autoimmune diseases. |
  | Decision Point Evaluation Method | - The Varelisa assay uses an OD cutoff for evaluation, and corresponding performance data show the comparability of results to the predicate device which uses a decision point method. |

2. Sample Sizes and Data Provenance for Test Set

• Sample Size for Test Set: Not explicitly stated as a single number. The document mentions a "data set including results obtained within a comparison study analyzing positive, equivocal and negative sera," and "results obtained for samples from apparently healthy subjects (normal population)." The specific number of samples in these comparison studies is not detailed.
• Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be clinical laboratory evaluations. The document refers to "the medical literature" and "scientific knowledge" as a basis for the intended use and performance expectations, implying a broader, though unspecified, provenance for general knowledge. The manufacturer is based in Germany.
• Retrospective/Prospective: Not explicitly stated. Given it's a 510(k) comparison study, it's often retrospective use of banked samples, but this is not confirmed.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

This device is an in-vitro diagnostic (IVD) immunoassay for autoantibodies. The "ground truth" for such devices typically relies on a combination of:

• Clinical diagnosis based on established medical criteria (e.g., for SLE, Antiphospholipid Syndrome).
• Results from a well-characterized predicate immunoassay or reference method.
• Clinical status of patients (e.g., "apparently healthy subjects").

The document does not mention the use of human experts (e.g., radiologists) establishing ground truth in the way it would for an imaging AI device. The ground truth seems to be implicitly derived from the clinical status of the patients and the results of the predicate device.

4. Adjudication Method for Test Set

No explicit adjudication method is described. The "ground truth" for an immunoassay comparison study is usually established by the clinical diagnosis of the patient and/or the result from the predicate device (or a gold standard if available), rather than a panel of expert reviewers adjudicating individual results.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC study was done. This type of study (evaluating human reader performance with and without AI assistance) is relevant for imaging AI devices that assist human interpretation. This device is an immunoassay kit for laboratory use and does not involve human "readers" in the diagnostic interpretation in the same way.

6. Standalone (Algorithm Only) Performance Study

Yes, a standalone performance was done in the sense that the device's performance was evaluated independently and then compared to a predicate device. The comparison studies evaluating "positive, equivocal and negative sera," "externally defined Calibrators," and "samples from apparently healthy subjects" represent evaluations of the device's standalone performance characteristics against expected outcomes or the predicate device. However, a specific "standalone" performance metric like sensitivity/specificity against a definitive gold standard not involving the predicate is not explicitly presented, as the emphasis is on substantial equivalence.

7. Type of Ground Truth Used

The ground truth appears to be a combination of:

• Clinical Status/Diagnosis: The intended use links the presence of antibodies to aiding in the diagnosis of thrombotic disorders related to Antiphospholipid Syndrome, SLE, or other autoimmune diseases. Samples were collected from "apparently healthy subjects" and presumably patients with known clinical conditions.
• Predicate Device Results: The entire study is a "comparison study analyzing positive, equivocal and negative sera" in relation to the predicate device, thereby using the predicate device's established performance as a de facto reference for "truth" in the context of substantial equivalence.

8. Sample Size for the Training Set

This document does not specify a separate "training set" or its size. This is typical for traditional IVDs like immunoassays, where extensive "training" in the machine learning sense is not performed. Assay development involves optimizing reagents, protocols, and cutoffs, which are different from training an ML algorithm on a dataset. The studies described are more akin to verification and validation.

9. How Ground Truth for the Training Set Was Established

As there is no "training set" in the context of an AI/ML algorithm, this question is not applicable. The development and optimization of the immunoassay would rely on established laboratory practices, chemical principles, and clinical samples previously characterized by the predicate device or clinical diagnosis.

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